Effects of alcohol and alcoholism on blood platelets are of interest, owing to potential effects of alcohol on the incidence of cardiovascular disorders involving platelets, including thrombotic and hemorrhagic stroke, atherosclerosis, and myocardial infarction. The popular view is that although abuse is detrimental, moderate consumption might be beneficial, but this is not well documented. The effects of alcohol and alcohol consumption on platelet function have received substantial attention, with mixed results. In general, platelet function is inhibited when alcohol is consumed or added in vitro, and platelet aggregation is measured by conventional turbidometric techniques in platelet rich plasma or washed platelets. Other studies show platelet activation in these preparations by alcohol, however. Two shortcomings in this area of research have been the lack of systematic study of alcohol's effects on platelets using consistent techniques, and the lack of physiological preparations for the study of platelet function. For these reasons, we have conducted preliminary studies utilizing whole blood platelet aggregation techniques, which allow physiological interaction between platelets, other formed elements, and plasma constituents. These studies show remarkably different results depending on the mode of alcohol exposure. In vitro alcohol, at physiologically attainable levels, produces platelet aggregation in rat or human blood by inducing release of ADP from red blood cells, which then activates platelets in a Ca++ dependent manner. Limited preliminary experiments suggest that chronic, low dose in vivo exposure of rats to alcohol, analogous to mild intoxication and alcohol dependence, might inhibit aggregation induced by collagen. The hypothesis is that effects of alcohol on platelets are modulated by other formed elements in blood, and are dependent on dose and duration of exposure. The specific aims are to determine effects of acute and chronic alcohol in rats on platelet functional parameters and bleeding time in whole blood; to determine the role of ambient alcohol level, as opposed to exposure history, on platelet function and bleeding time; to critically evaluate the role of erythrocyte-platelet interactions on platelet functional effects of alcohol; and to evaluate the potential role of other formed elements on platelet effects of alcohol. These studies will be performed in rat models of acute and chronic alcohol consumption via inhalation, which results in a predictable level of blood alcohol, using ex vivo whole blood platelet aggregation techniques. In vitro studies will also be performed in human blood.